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  • Boyette Brask posted an update 1 day, 17 hours ago

    Decreased d-[3-11C]alanine uptake was also observed in antibiotic-sensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of d-[3-11C]alanine uptake was seen in rodent models of discitis-osteomyelitis and P. aeruginosa pneumonia. These data provide strong justification for clinical translation of d-[3-11C]alanine to address a number of important human infections. Copyright © 2020 American Chemical Society.Protein glycosylation is a common post-translational modification that influences the functions and properties of proteins. Despite advances in methods to produce defined glycoproteins by chemoenzymatic elaboration of monosaccharides, the understanding and engineering of glycoproteins remain challenging, in part, due to the difficulty of site-specifically controlling glycosylation at each of several positions within a protein. Here, we address this limitation by discovering and exploiting the unique, conditionally orthogonal peptide acceptor specificities of N-glycosyltransferases (NGTs). We used cell-free protein synthesis and mass spectrometry of self-assembled monolayers to rapidly screen 41 putative NGTs and rigorously characterize the unique acceptor sequence preferences of four NGT variants using 1254 acceptor peptides and 8306 reaction conditions. We then used the optimized NGT-acceptor sequence pairs to sequentially install monosaccharides at four sites within one target protein. This strategy to site-specifically control the installation of N-linked monosaccharides for elaboration to a variety of functional N-glycans overcomes a major limitation in synthesizing defined glycoproteins for research and therapeutic applications. Copyright © 2020 American Chemical Society.The synthesis and dynamic nature of macromolecular systems controlled by rotaxane macromolecular switches are introduced to discuss the significance of rotaxane linking of polymer chains and its topological switching. Macromolecular switches have been synthesized from macromolecular [2]rotaxanes (M2Rs) using sec-ammonium salt/crown ether couples. The successful synthesis of M2Rs possessing a single polymer axle and one crown ether wheel, constituting a key component of the macromolecular switch, has allowed us to develop various unique applications such as the development of topology-transformable polymers. Polymer topological transformations (e.g., linear-star and linear-cyclic) are achieved using rotaxane-linked polymers and rotaxane macromolecular switches. The pronounced dynamic nature of these polymer systems is sufficiently interesting to design sophisticated stimuli-responsive molecules, polymers, and materials. Copyright © 2020 American Chemical Society.Mechanically interlocked molecules are perhaps best known as components of molecular machines, a view further reinforced by the Nobel Prize in 2016 to Stoddart and Sauvage. Despite amazing progress since these pioneers of the field reported the first examples of molecular shuttles, genuine applications of interlocked molecular machines remain elusive, and many barriers remain to be overcome before such molecular devices make the transition from impressive prototypes on the laboratory bench to useful products. Here, we discuss simplicity as a design principle that could be applied in the development of the next generation of molecular machines with a view to moving toward real-world applications of these intriguing systems in the longer term. Copyright © 2020 American Chemical Society.Nanoparticles have been widely used in tumor targeted drug delivery, while the antitumor effects are not always satisfactory due to the limited penetration and retention. As we all know, there is a paradox that nanoparticles with large sizes tend to distribute around tumor blood vessels rather than penetrate into tumor parenchyma, while smaller sizes can penetrate deeply but with poor tumor retention. In recent days, an intelligent, size-tunable strategy provided a solution to determine the size problem of nanoparticles and exhibited good application prospects. In this review, we summarize series of stimuli-induced aggregation and shrinkage strategies for tumor targeted drug delivery, which can significantly increase the retention and penetration of nanodrugs in tumor sites at the same time, thus promoting treatment efficacy. Internal (enzymes, pH, and redox) and external (light and temperature) stimuli are introduced to change the morphology of the original nanodrugs through protonation, hydrophobization, hydrogen bond, π-π stacking and enzymolysis-resulted click reactions or dissociation, etc. Apart from applications in oncotherapy, size-tunable strategies also have a great prospect in the diagnosis and real time bioimaging fields, which are also introduced in this review. check details Finally, the potential challenges for application and future directions are thoroughly discussed, providing guidance for further clinical transformation. Copyright © 2020 American Chemical Society.Over the past decade, studies on microRNA (miRNA) and cancer quickly became known. miRNAs are small non-coding RNAs that play a vital role in regulation of gene expression. In the present study, the expression of miR-27b, miR-29a, and miR-155, their prognostic roles, and their potential targets in chronic lymphocytic leukemia (CLL) and breast cancer (BC) by qRT-PCR were investigated. In two case-control studies, qRT-PCR was used to analyze the peripheral blood serum of 15 CLL patients and tissue samples of 15 BC patients for the expression of miR-27b, miR-29a, and miR-155. miRNA expression levels were calculated using the qRT-PCR method. The results revealed a significant increase in the expression of all miRNAs in patients with BC and CLL compared with respective healthy groups (p  less then 0.001). In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (p  less then 0.05), miR-155 and miR-27b (p  less then 0.01), and miR-27b and miR-29a (p  less then 0.001). In CLL patients, a significant difference between expression of both miR-27b and miR-29a compared with expression of miR-155 (p  less then 0.001) was found. Furthermore, a significant association between miR-155 and prevascular invasion was found. Significantly, elevated circulating miRNAs were shown to be BC specific and could differentiate BC tissues from the controls. It was demonstrated that miRNAs used in this study and their expression profiles can be developed as biomarkers for early diagnosis and prognosis of CLL and BC. Further studies utilizing a larger test group of patients would provide identification of miRNAs as key players in intercellular interactions. © 2020.

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